title: Gastric cancer progression may involve a shift in HLA-E profile from an intact heterodimer to β2-microglobulin-free monomer.
abstract: Phenotypic expression of human leukocyte antigen (HLA)-E on the surface of tumor lesions includes intact heterodimer [HLA-E heavy chain and β2-microglobulin (β2m)] and β2m-free monomer. Anti-HLA-E monoclonal antibodies (mAbs), MEM-E/02 or 3D12 bind to the peptide sequences in β2m-free HLA-E, which is common and shared with HLA-Ia monomers. A newly developed monospecific anti-HLA-E mAb (TFL-033) recognizes HLA-E-restricted peptide sequences on α1 and α2 helices away from β2-m-site. Tumor progression may involve shedding of β2-m from HLA-E or overexpression of β2m-free monomers. There is a need to identify and distinguish the different phenotypic expression of HLA-E, particularly the intact heterodimer from the β2m-free monomer on the surface of tumor lesions. Because of the unique peptide-binding affinities of the mAbs, it is hypothesized that TFL-033 and MEM-E/02 may distinguish the phenotypic expressions of cell surface HLA-E during stages of tumor progression. Only TFL-033 stained diffusely the cytoplasm of normal mucosa. The incidence and intensity of TFL-033 staining of the cell surface in early stages, poorly or undifferentiated and non-nodal lesions and in diffuse carcinoma is greater than that of MEM-E/02. Whereas MEM-E/02 stained terminal stages, adenocarcinoma and lymph node metastatic lesions intensely, either owing to increased expression of β2m-free HLA-E with tumor progression or owing to expression of HLA-Ia molecules. Our study evaluates the relative diagnostic potential of HLA-E-monospecific TFL-033 and the HLA-Ia-reactive MEM-E/02 for determining the specific distribution and immunodiagnosis of different phenotypic expression HLA-E in tumor lesions, and the structural and functional alterations undergone by HLA-E during tumor progression.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA; Department of Surgery, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Mepur H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Freitas
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawakita
authors.forename: Vadim
authors.initials: V
authors.lastname: Jucaud
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000097625:HLA-E Antigens
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D000097625:HLA-E Antigens
keywords: HLA-E; adenocarcinoma; anti-HLA-E antibodies; carcinoma; gastric cancer; gastric mucosa; heterodimer; monomer; tumor progression; β2-microglobulin